WO2011043272A1 - LIGAND POUR CATALYSEUR DE SYNTHÈSE ASYMÉTRIQUE ET PROCÉDÉ POUR LA PRODUCTION D'UN COMPOSÉ CYCLIQUE α-ALCÉNYLIQUE L'UTILISANT - Google Patents

LIGAND POUR CATALYSEUR DE SYNTHÈSE ASYMÉTRIQUE ET PROCÉDÉ POUR LA PRODUCTION D'UN COMPOSÉ CYCLIQUE α-ALCÉNYLIQUE L'UTILISANT Download PDF

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WO2011043272A1
WO2011043272A1 PCT/JP2010/067279 JP2010067279W WO2011043272A1 WO 2011043272 A1 WO2011043272 A1 WO 2011043272A1 JP 2010067279 W JP2010067279 W JP 2010067279W WO 2011043272 A1 WO2011043272 A1 WO 2011043272A1
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formula
ligand
represented
alkenyl
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雅人 北村
田中　慎二
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国立大学法人名古屋大学
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    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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    • C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
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    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/32—Addition reactions to C=C or C-C triple bonds
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    • B01J2531/02—Compositional aspects of complexes used, e.g. polynuclearity
    • B01J2531/0261—Complexes comprising ligands with non-tetrahedral chirality
    • B01J2531/0266—Axially chiral or atropisomeric ligands, e.g. bulky biaryls such as donor-substituted binaphthalenes, e.g. "BINAP" or "BINOL"
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Definitions

  • the present invention relates to a ligand for asymmetric synthesis catalyst and a method for producing ⁇ -alkenyl cyclic compounds using the same. More specifically, the present invention relates to a ligand having a specific structure, easily coordinated to Ru contained in the catalyst precursor, and useful for the production of chiral ⁇ -alkenyl cyclic compounds, and these catalyst precursors. The present invention relates to a method for producing ⁇ -alkenyl cyclic compounds in which a specific allyl alcohol is subjected to a dehydration cyclization reaction in the presence of a catalyst comprising a ligand for an asymmetric synthesis catalyst.
  • optically active substances having an asymmetric carbon atom among physiologically active substances there are many optically active substances having an asymmetric carbon atom among physiologically active substances, and it is important to obtain an optically active substance having a predetermined steric structure.
  • Examples of a method for obtaining this optically active substance include a method of synthesizing a racemate and then fractionating an optically active substance having a predetermined steric structure by optical resolution or the like.
  • this method is low in efficiency because chemical conversion is necessary. For this reason, research and development of asymmetric synthesis methods capable of selectively synthesizing optically active substances having a predetermined steric structure are in progress.
  • One of the most important structural units in optically active substances such as polycyclic ethers includes cyclic ethers having an asymmetric center (for example, see Non-Patent Document 1). Of the many basic structures reported so far, ⁇ -alkenyl substituted cyclic ethers are known to be most useful. Further, with regard to this ⁇ -alkenyl-substituted cyclic ether, a catalyst having particularly high selectivity has attracted attention.
  • Wacker-type oxidized cyclization of orthoallyl or homoallylphenol derivatives see, for example, Non-Patent Document 2
  • ⁇ -hydroxyallyl ⁇ -Trost type intramolecular allylation using esters for example, see Non-Patent Document 3
  • addition of alcohols to alkynes for example, see Non-Patent Document 4
  • addition of alcohols to allenes A synthesis method such as (see, for example, Non-Patent Document 5) is known.
  • the present invention provides a ligand having a specific structure, easily coordinated to Ru of a catalyst precursor, and useful for the production of chiral ⁇ -alkenyl cyclic compounds, and asymmetric synthesis with these catalyst precursors
  • An object of the present invention is to provide a method for producing an ⁇ -alkenyl cyclic compound in which a specific allyl alcohol is subjected to a dehydration cyclization reaction in the presence of a catalyst comprising a catalyst ligand.
  • the present invention is as follows.
  • R 1 is —Cl or —Br
  • R 2 is —CH 3 or —CF 3
  • R 3 is —CH 2 —CH ⁇ CH 2 or —H.
  • the R 1 is —Cl and the R 2 is —CH 3, which is represented by the formula (1) or the formula (2);
  • the allyl alcohol is the ⁇ -hydroxyallyl alcohol
  • the cyclic compound is a cyclic ether having a 5-membered ring ether structure or a 6-membered ring ether structure.
  • the ⁇ -hydroxyallyl alcohol represented by the formula (6) is a compound of the following (a) to (l): A process for producing an ⁇ -alkenyl cyclic compound as described in 1. above. (A); R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —H, and R 5 is —H.
  • R 6 in the formula (6) is —CH 2 CH 2 —, R 4 is —H, and R 5 is —H.
  • C R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —CH 3 , and R 5 is —H.
  • D R 6 in the formula (6) is —CH 2 CH 2 —, R 4 is —CH 3 , and R 5 is —H.
  • E R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —C 2 H 5 , and R 5 is —H.
  • R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —nC 5 H 11 , and R 5 is —H.
  • G R 6 in the above formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —CH 2 (iC 3 H 7 ), and R 5 is —H.
  • H R 6 in the formula (6) is —CH 2 CH 2 CH 2 —, R 4 is —H, and R 5 is —CH 3.
  • R 6 in the formula (6) is —C (CH 3 ) 2 CH 2 CH 2 —, R 4 is —H, and R 5 is —H.
  • HO—R 6 in the formula (6) is represented by the following formula (7), R 4 is —CH 3 , and R 5 is —H.
  • K HO—R 6 in the formula (6) is represented by the following formula (8), R 4 is —H, and R 5 is —CH 3.
  • Bn is a benzyl group (C 6 H 5 CH 2 —).
  • L HO—R 6 in the formula (6) is represented by the following formula (9), R 4 is —CH 3 , and R 5 is —H. 6).
  • the ratio 3 (M 1 / M 2 ) of the number of moles (M 1 ) of the ⁇ -hydroxyallyl alcohols to the number of moles (M 2 ) of the ligand for asymmetric synthesis catalyst is 100 to 1000 .
  • To 5. The method for producing an ⁇ -alkenyl cyclic compound according to any one of the above. 7). 2. The temperature of the reaction is 80 to 120 ° C. To 6. The method for producing an ⁇ -alkenyl cyclic compound according to any one of the above. 8). 2. The reaction solvent is dimethylacetamide. To 7. The method for producing an ⁇ -alkenyl cyclic compound according to any one of the above.
  • the ligand for an asymmetric synthesis catalyst of the present invention easily coordinates to Ru of a catalyst precursor having a specific structure to form an asymmetric synthesis catalyst, and this catalyst dehydrates specific allyl alcohols. Cyclization can be carried out to produce chiral ⁇ -alkenyl cyclic compounds with high yield and high enantioselectivity. In the case where R 1 is —Cl and R 2 is —CH 3 and is represented by the formula (1) or (2), the chiral ⁇ can be obtained with higher yield and higher selectivity. -Alkenyl cyclic compounds can be prepared.
  • ⁇ -alkenyl cyclic compounds of the present invention many kinds of allyl alcohols are subjected to a dehydration cyclization reaction with simple operations and steps, and a chiral ⁇ with high yield and high enantioselectivity. -Alkenyl cyclic compounds can be easily produced.
  • the allyl alcohol is ⁇ -hydroxyallyl alcohol and the cyclic compound is a cyclic ether having a 5-membered ring ether structure or a 6-membered ring ether structure
  • many kinds of ⁇ -hydroxyallyl alcohols are used.
  • reaction temperature is 80 to 120 ° C.
  • ⁇ -alkenyl cyclic compounds can be efficiently produced with high yield and selectivity without requiring a long time for the reaction.
  • the reaction solvent is dimethylacetamide, a stable reaction is possible, and ⁇ -alkenyl cyclic compounds can be efficiently produced with high yield and selectivity.
  • 1 is a 1 H-NMR spectrum of allyl 6- (2-chloronaphthalen-1-yl) -5-methylpyridine-2-carboxylate.
  • FIG. 6 is a 13 C-NMR spectrum of allyl 6- (2-chloronaphthalen-1-yl) -5-methylpyridine-2-carboxylate.
  • 1 is a 1 H-NMR spectrum of an ⁇ -alkenyl cyclic ether produced using a compound represented by the above formula (a) as ⁇ -hydroxyallyl alcohol.
  • 3 is a 13 C-NMR spectrum of an ⁇ -alkenyl cyclic ether produced using a compound represented by the formula (a) as ⁇ -hydroxyallyl alcohols.
  • Ligand for asymmetric synthesis catalyst of the present invention (hereinafter sometimes simply referred to as ligand) is one of the above formulas (1) to (4). It is represented by one.
  • R 1 is —Cl (chlorine atom) and Any of -Br (bromine atom) may be used, but -Cl is preferred.
  • R 2 may be either —CH 3 (methyl group) or —CF 3 , but is preferably —CH 3 .
  • R 3 may be either —CH 2 —CH ⁇ CH 2 (allyl group) or —H (hydrogen atom), but is preferably —CH 2 —CH ⁇ CH 2 . That is, an allyl ester type ligand is preferable to an acid type. Therefore, the ligand is preferably an allyl ester type ligand in which R 1 is —Cl and R 2 is —CH 3 in the formulas (1) and (2).
  • R 1 is —Cl.
  • R 2 is preferably —CH 3
  • R 3 is preferably —CH 2 —CH ⁇ CH 2 . That is, an allyl ester type ligand is preferable to an acid type. Accordingly, in the formulas (3) and (4), an allyl ester type ligand in which R 1 is —Cl and R 2 is —CH 3 is preferable.
  • the ligand for an asymmetric synthesis catalyst of the present invention is a catalyst precursor represented by the above formula (5), that is, [Ru (C 5 H 5 ) (CH 3 CN) 3 ] PF 6 [the following formula ( 10), which has a structural portion in which three acetonitriles (CH 3 CN) are coordinated to Ru. ]
  • the ligand and catalyst precursor of the present invention may be used by adding a solvent to a solid ligand and a solid catalyst precursor and mixing them, or a ligand dissolved in a solvent and a solid catalyst precursor.
  • each solvent may be the same and may differ.
  • the prepared ligand may be isolated once and used by dissolving in a solvent at the time of use, or may be used as manufactured, that is, as dissolved in the solvent used at the time of manufacture. [In the formula (10), the broken line between Ru and N represents a coordination bond. ]
  • allyl alcohol is an ⁇ -hydroxyallyl alcohol represented by the formula (6)
  • an ⁇ -alkenyl cyclic ether having a 5-membered ring ether structure or a 6-membered ring ether structure can be produced. it can.
  • R 4 may be either —H or an alkyl group having 1 to 5 carbon atoms, —H It is preferable that When R 4 is an alkyl group, the number of carbon atoms may be 1 to 5, but is preferably —CH 3 having 1 carbon atom or —C 2 H 5 (ethyl group) having 2 carbon atoms, In particular, —CH 3 having 1 carbon atom is more preferable. Furthermore, this alkyl group may be either a linear alkyl group or a branched alkyl group. R 5 may be either —H or —CH 3 , but is preferably —H.
  • R 6 is a divalent organic group in which the oxygen atom of the hydroxyl group at the ⁇ -position is bonded to the carbon atom to which R 5 is bonded to form a 5-membered ether structure or a 6-membered ether structure. It is.
  • the ⁇ -hydroxyallyl alcohols used as starting materials are ⁇ -alkenyl cyclic ethers having R 4 , R 5 and R 6 as described above and having a 5-membered ring ether structure or a 6-membered ring ether structure.
  • the starting material is not particularly limited as long as it can be obtained, and various starting materials can be used.
  • R 6 in the formula (6) is —CH 2 CH 2 —, —CH 2 CH 2
  • the structural portion represented by CH 2 — or —C (CH 3 ) 2 CH 2 CH 2 — and HO—R 6 in the formula (6) are represented by the formula (7), the formula (8) or the formula (9 ⁇ -hydroxyallyl alcohols, which are structural moieties represented by
  • allyl alcohols Meldrum's acid type allyl alcohols, sulfonylaminoallyl alcohols and carboxyallyl alcohols can also be used.
  • ⁇ -hydroxyallyl alcohols the intramolecular dehydration cyclization reaction of the starting material
  • ⁇ -alkenyl cyclic compounds can be produced.
  • the hydrogen atom of the substituent reacts with the hydroxyl group, and ⁇ -alkenyl cyclic compounds are formed by dehydration cyclization.
  • the substituent has a hydrogen atom, an oxygen atom, and a carbon atom, and the hydrogen atom that participates in the dehydration reaction is bonded to the carbon atom.
  • intramolecular dehydration cyclization reaction is promoted in a reaction system using the ligand for asymmetric synthesis catalyst of the present invention and a specific catalyst precursor, and ⁇ -alkenyl cyclic compounds Can be manufactured efficiently.
  • what is bonded to the carbon atom of the skeleton part excluding the substituent may be a hydrogen atom or an alkyl group.
  • the substituent has a hydrogen atom, a nitrogen atom, a sulfur atom, and an oxygen atom, and the hydrogen atom that participates in the dehydration reaction is bonded to the nitrogen atom.
  • intramolecular dehydration cyclization reaction is promoted in a reaction system using the ligand for asymmetric synthesis catalyst of the present invention and a specific catalyst precursor, and ⁇ -alkenyl cyclic compounds Can be manufactured efficiently.
  • what is bonded to the carbon atom of the skeleton part excluding the substituent may be a hydrogen atom or an alkyl group.
  • the substituent has a hydrogen atom, an oxygen atom, and a carbon atom, and the hydrogen atom that participates in the dehydration reaction is bonded to the oxygen atom.
  • intramolecular dehydration cyclization reaction is promoted in a reaction system using the ligand for asymmetric synthesis catalyst of the present invention and a specific catalyst precursor, and ⁇ -alkenyl cyclic compounds Can be manufactured efficiently.
  • what is bonded to the carbon atom of the skeleton part excluding the substituent may be a hydrogen atom or an alkyl group.
  • an asymmetric synthesis catalyst ligand and a catalyst precursor are mixed to form an asymmetric synthesis catalyst, and then reacted with a blended starting material.
  • ⁇ -alkenyl cyclic compounds are produced.
  • the method for mixing the ligand and the catalyst precursor is not particularly limited as described above, but a method in which a solution in which the ligand is dissolved is added to and mixed with the solid catalyst precursor charged into the reactor is preferable.
  • the starting material is produced as a liquid or solid stereoisomer, and is dissolved in an appropriate solvent when used. Further, the solution in which the starting material is dissolved is blended with the solution in which the catalyst system is formed by the ligand and the catalyst precursor, and ⁇ -alkenyl cyclic compounds are generated.
  • the solvent for dissolving the ligand and the solvent for dissolving the catalyst precursor may be the same or different as described above, but the solvent for dissolving the starting material is also the catalyst. It may be the same as or different from at least one of the solvent for dissolving the precursor and the solvent for dissolving the ligand.
  • the solvent include dimethylacetamide (DMA), dimethylformamide (DMF), tetrahydrofuran (THF), cyclopentyl methyl ether (CPME), dioxane, dichloromethane, acetone, toluene, methyl alcohol, ethyl alcohol, t-butyl alcohol, Examples include i-propyl alcohol, acetic acid, water and the like.
  • solvents for dissolving the catalyst precursor and the ligand are preferable as solvents for dissolving the catalyst precursor and the ligand, respectively.
  • a solvent for dissolving the starting material usually a solvent serving as a reaction solvent, DMA, DMF, THF, CPME, t-butyl alcohol and the like are preferable, and DMA is more preferable.
  • the ratio (M 1 / M 2 ) of the number of moles of starting material (M 1 ) to the number of moles of ligand (M 2 ) can produce the desired ⁇ -alkenyl cyclic compounds.
  • the ratio is preferably 90% or more, particularly 95% or more, and more preferably 99% or more, practically, although the conversion rate from the starting material to ⁇ -alkenyl cyclic compounds is not particularly limited.
  • the ratio (M 1 / M 2 ) is preferably 50 to 5000, particularly 70 to 3000, and more preferably 100 to 1000.
  • the conversion can be sufficiently increased with a very small amount of catalyst as compared with the conventional method.
  • the reaction conditions are not particularly limited, and the reaction conditions depend on the type of the ligand and the starting material, particularly the type of the starting material, etc. It is preferable to adjust appropriately.
  • the reaction temperature depends on the reaction time, but from a practical point of view, it is preferably 50 to 150 ° C., particularly 70 to 130 ° C., more preferably 80 to 120 ° C.
  • the reaction time can be 0.1 to 3 hours, particularly 0.1 to 1.5 hours when the reaction temperature is 80 to 120 ° C.
  • the reaction temperature is a low temperature of less than 80 ° C., By making the reaction time longer, the conversion rate from the starting material to the ⁇ -alkenyl cyclic compounds can be sufficiently increased to 99% or more.
  • the atmosphere during the reaction is an inert atmosphere, and this inert atmosphere is not particularly limited.
  • the atmosphere can be a nitrogen gas atmosphere or a rare gas atmosphere such as argon gas, helium gas, or neon gas.
  • a conventionally known method such as distillation, adsorption, extraction, recrystallization, or a combination of these methods is used.
  • the desired ⁇ -alkenyl cyclic compounds can be recovered and purified.
  • the target optically active substance can be further purified by optical resolution or the like, if necessary.
  • a mechanism in which an ⁇ -alkenyl cyclic compound is formed by forming a catalyst system using a ligand and a catalyst precursor, and mixing and reacting with a specific allyl alcohol is, for example,
  • allyl alcohol is ⁇ -hydroxyallyl alcohol, it is considered as follows.
  • (R) -Cl-Naph-PyCOOH [acid type ligand of formula (1)] is complexed with [CpRu (CH 3 CN) 3 ] PF 6 (catalyst precursor) to form [CpRu ((R ) -Cl-Naph-PyCOOH)] PF 6 to capture the allyl alcohol substrate, resulting in a sub / cat complex (starting material / catalyst complex) [see formula (11) below].
  • the electrophilicity of the ⁇ carbon is remarkably improved by the hydrogen bond between the proton of the carboxylic acid of the ligand and the hydroxy group of the ⁇ -hydroxyallyl alcohol.
  • the ⁇ -allyl complex (R, R Ru ) -Asyn, anti [see the following formula (12)] (syn is the positional relationship between the ⁇ -allyl 2-position proton and the 3-position substituent, and anti is the carboxylate ligand and the ⁇ -allyl 3-position substituent.
  • the (R) -Naph-PyCOOH / CpRu catalyst gives an S product in preference to the inside attack capable of hydrogen bonding between the oxygen atom of the carboxylate ligand and the ⁇ -hydroxy proton.
  • the S body is generated by the outside attack via the (R, S Ru ) Asyn, syn diastereomer.
  • there are two diastereomeric intermediates such as steric repulsion between the Cp, ⁇ allyl, and PyCOO moieties on the Ru atom, hydrogen bonding between CpH / Cl, and CH- ⁇ interaction between benzene rings / CpH.
  • Example 1 [Preparation of allyl 6- (2-chloronaphthalen-1-yl) -5-methylpyridine-2-carboxylate]
  • 2- (2-chloronaphthalen-1-yl) -3-methylpyridine To a dried Schlenk tube with a capacity of 250 mL, 2- (2-triethylsilyl) naphthalen-1-yl) -3-methyl 8 g (24 mmol) of pyridine and 48 mL of dichloromethane were added, and the temperature was lowered to ⁇ 78 ° C.
  • this oily substance was purified by silica gel column chromatography (100 g, the solvent was hexane and ethyl acetate in a mass ratio of 5: 1), and 856 mg (yield 93%) of 6- (2-chloronaphthalen-1-yl) was obtained. ) -5-methylpyridine-2-carbonitrile was obtained.
  • optical purity of each enantiomer separated was determined by high performance liquid chromatography [column: CHIRALCEL OD-H (manufactured by DAICEL, ⁇ 0.46 cm ⁇ 25 cm), solvent: hexane and 2-propanol at a mass ratio of 5: 1. Mixed solvent, flow rate: 1 mL / min, wavelength of light source: 254 nm] [(R) -isomer peaked at 14.1 min, (S) -isomer peaked at 25.0 min. It was. ].
  • a ligand in which —Cl is replaced with a phenyl group includes 3-methyl-2- (2-phenylnaphthalen-1-yl) pyridine and 5-methyl- Prepared by a synthesis method via 6- (2-phenylnaphthalen-1-yl) pyridine-2-carbonitrile. Further, the racemate of each ligand was separated into (R) -form and (S) -form by high performance liquid chromatography as in the case of the ligand of the present invention.
  • Example 2 [Production of ⁇ -alkenyl cyclic ethers] (Experimental Examples 1 to 3) 4.34 mg (10.0 ⁇ mol) of the catalyst precursor represented by the formula (5) was charged into a 50-mL Schlenk tube with a Young valve, which was dried and filled with Ar, and a magnetic stir bar was added.
  • the ligand prepared in Example 1 [as shown in Table 1, the acid form of Formula (1) (Experimental Example 1) and the acid form of Formula (2) (Experimental Example 2), and the formula (1) Allyl ester type (Experimental Example 3)] 1.00 mL (10.0 mM dichloromethane solution was used. Therefore, the amount of ligand was 10.0 ⁇ mol) was added by an airtight syringe.
  • Compound (a) which is ⁇ -hydroxyallyl alcohol used as a starting material for producing ⁇ -alkenyl cyclic ethers, was prepared as follows. Synthesis by a conventionally known method of Horner-Wadsworth-Emmons transformation between the 2nd and 3rd carbons using the corresponding ⁇ , ⁇ -unsaturated esters, followed by DIBAL-H transformation did. Stereoisomers were separated by silica gel column chromatography at the stage of ⁇ , ⁇ -unsaturated esters. Compounds (b) to (l) ⁇ -hydroxyallyl alcohols used as starting materials in Example 4 to be described later, and compounds as comparative examples in which R 6 has one more methylene group than compound (a) was produced in the same manner.
  • Example 3 (Experimental Examples 4 to 22) In Example 2, various conditions were changed as shown in Table 1 to produce an ⁇ -alkenyl cyclic ether represented by the formula (14).
  • Experimental Example 4 The same as Experimental Example 3, except that the starting material concentration was 1000 mM and the ligand concentration was 10 mM.
  • Experimental Example 5 The same as Experimental Example 3, except that the ligand concentration was 0.1 mM, that is, the catalyst amount was 1/10.
  • Experimental Example 6 The same as Experimental Example 3, except that the starting material concentration was 1000 mM, that is, the starting material amount was increased 10 times and the ligand was an allyl ester type of the formula (2).
  • Experimental Example 7 The same as Experimental Example 3, except that the reaction temperature was 50 ° C.
  • Experimental Example 8 The same as Experimental Example 3 except that the solvent was DMF.
  • Experimental Example 9 The same as Experimental Example 3, except that the solvent was CH 3 CN.
  • Experimental Example 10 The same as Experimental Example 3, except that the solvent was acetone.
  • Experimental Example 11 The same as Experimental Example 3, except that the solvent was THF.
  • Experimental Example 12 The same as Experimental Example 3, except that the solvent was CPME.
  • Experimental Example 13 The same as Experimental Example 3 except that the solvent was dioxane.
  • Experimental Example 14 The same as Experimental Example 3, except that the solvent was CH 2 Cl 2 .
  • Experimental Example 15 The same as Experimental Example 3, except that the solvent was toluene.
  • Experimental Example 16 The same as Experimental Example 3 except that the solvent was tC 4 H 9 OH.
  • Experimental Example 17 The same as Experimental Example 16, except that the starting material concentration was 1000 mM, that is, the starting material amount was 10 times.
  • Experimental Example 18 The same as Experimental Example 3, except that the solvent was iC 3 H 7 OH.
  • Experimental Example 19 The same as Experimental Example 3, except that the solvent was C 2 H 5 OH.
  • Experimental Example 20 The same as Experimental Example 3, except that the solvent was CH 3 OH.
  • Experimental Example 21 The same as Experimental Example 3, except that the solvent was H 2 O.
  • Experimental Example 22 The same as Experimental Example 3, except that the solvent was CH 3 COOH.
  • the conversion and enantioselectivity in Experimental Examples 4 to 22 were determined in the same manner as described above. The results of Example 2 and Example 3 are also shown in Table 1.
  • Experimental Example 23 which was reacted in the same manner as Experimental Example 3, except that a ligand in which —Cl was replaced with —CH 3 in the allyl ester type of the formula (1), was used. 23, except that the ligand concentration of 0.1 mM was used in Experimental Example 24 and the allyl ester type of the formula (1) was replaced with a ligand in which —Cl was replaced with a phenyl group. The reacted ⁇ -alkenyl cyclic ether of Experimental Example 25 was produced. Further, the conversion rates in Experimental Examples 23 to 25 and the enantioselectivity in Experimental Example 23 were determined in the same manner as described above. The production conditions and results of Experimental Examples 23 to 25 are shown in Table 1.
  • Example 1 using the acid form of the formula (1) as the ligand and DMA as the solvent, and the experiment using the acid type of the formula (2) as the ligand and DMA as the solvent
  • the conversion is 99% or more
  • er is 97: 3 or 3:97, indicating that both the conversion and the selectivity are high.
  • Experimental Example 3 using the allyl ester type of the formula (1)
  • Experimental Example 4 using the starting material and the ligand having a 10-fold concentration in Experimental Example 3, and in Experimental Example 3, the catalyst amount was reduced to 1/10.
  • the ligand was an allyl ester type of the formula (2), the catalyst amount was kept as it was and the starting material was 10 times the amount. Has been obtained.
  • Experimental Example 25 in which the reaction was carried out in the same manner as Experimental Example 3, except that a ligand in which —Cl was replaced with a phenyl group in the allyl ester type of the formula (1) was used, Experimental Example 3 as well as Experimental Example 3 It can be seen that the conversion is even lower than 23, and that a ligand in which —Cl is replaced with a phenyl group cannot be put to practical use.
  • Example 4 (Production of various ⁇ -alkenyl cyclic ethers using various starting materials) As shown in Table 2, using the compounds (a) to (l), the corresponding ⁇ -alkenyl cyclic ether represented by the formula (14) and the experiments represented by the following formulas (15) to (25) The ⁇ -alkenyl cyclic ethers of Examples 26-37 were prepared. The reaction was carried out under the same conditions as in Example 2 except for the following points: the starting material was 100 mM, the ligand was 1 mM, the solvent was DMA, the reaction temperature was 100 ° C., and the reaction time was 1 hour. It carried out in.
  • the difference from the standard conditions is (1) The concentration of the starting material was 1000 mM in Experimental Example 26 using the compound (a). (2) The reaction time was 3 hours in Experimental Example 32 using the compound (g). (3) In Experimental Example 33 using the compound (h), the reaction temperature was 70 ° C., and the reaction time was 10 hours. (4) In Experimental Examples 35 to 37 using compounds (j) to (l), the solvent was a mixed solvent of t-C 4 H 9 OH and DMA having a mass ratio of 10: 1. (5) In Experimental Example 36, the reaction time was set to 24 hours after the above (5). It is. The enantioselectivity (er) in Experimental Examples 26 to 37 was determined in the same manner as described above.
  • the isolated yield was determined by partitioning the reaction solution with 3 mL of a mixed solvent of pentane and ether (3: 1 by mass) and 5 mL of water, filtering the organic layer with silica gel, and then at 0 ° C. and 50 mmHg. The product was isolated and weighed (except for experimental examples 27 and 29). The results are also shown in Table 2.
  • Bn is a benzyl group (C 6 H 5 CH 2 —).
  • Example 5 Corresponding ⁇ -alkenyl cyclic compounds were prepared using various allyl alcohols having different substituents.
  • Experimental Example 39 (Dehydrative cyclization reaction of Meldrum's acid type allyl alcohol) In a reaction tube equipped with a Young valve having a capacity of 20 mL, a 300 ⁇ L (333 mM concentration solution) of a dichloromethane solution of 2- (E) -5-hydroxypent-3-en-1-ylmeldrum acid as a starting material was used under an argon stream. Therefore, the amount of starting material is 100 ⁇ mol). The solution was concentrated under reduced pressure, and 1.00 mL of dichloromethane was added, followed by freeze degassing three times.
  • the enantiomeric ratio was also determined by gas chromatographic analysis of the product [column; CHIRALDEX B-PM (0.25 mm ⁇ 0.125 ⁇ m ⁇ 30 m), temperature; 100 ° C., split ratio; 100: 1]. As a result, the ratio of the integrated values of the respective peaks was 83:17.
  • the amount of the ligand was 10.0 ⁇ mol) was added.
  • the solution was then carefully concentrated under reduced pressure and brought to atmospheric pressure with argon.
  • the starting material solution prepared as described above was then added using a cannula and stirred in an oil bath at 100 ° C. After 20 minutes, the reaction mixture was subjected to silica gel column chromatography (sample; 30 g, developing solvent; ether) to isolate 4-ethenylbutyrolactone. Thereafter, Kugelrohr distillation (35 ° C., 0.01 mmHg) was performed to obtain a colorless oil (75.6 mg, addition rate: 70%).
  • the enantiomeric ratio was also determined by gas chromatography analysis of the product [column; CHIRALDEX B-PM (0.25 mm ⁇ 0.125 ⁇ m ⁇ 30 m), temperature: held at 40 ° C. for 5 minutes, heating rate 1 ° C./min, Hold at 65 ° C. for 65 minutes, split ratio; 100: 1].
  • the ratio of the integrated values of each peak was 99: 1.
  • the present invention is not limited to the description of the above-described embodiment, and various modifications can be made within the scope of the present invention according to the purpose, application, and the like.
  • the ligand and the catalyst precursor are mixed and then the starting material is blended and reacted.
  • the ligand, the catalyst precursor, and the starting material are simultaneously mixed with an appropriate reaction solvent. It is also possible to produce ⁇ -alkenyl cyclic compounds by dissolving them in Further, a solution in which a ligand and a catalyst precursor are dissolved can be blended and reacted with a solution in which a starting material is dissolved.

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Abstract

L'invention porte sur un ligand pour un catalyseur de synthèse asymétrique; et un procédé de production d'un composé cyclique α-alcénylique utilisant le ligand. De façon spécifique, l'invention porte sur un ligand pour un catalyseur de synthèse asymétrique, qui est représenté par l'une quelconque des formules (1) à (4) [dans lesquelles R1 représente -Cl ou -Br; R2 représente -CH3 ou -CF3 ; et R3 représente -CH2-CH=CH2 ou -H]; et un procédé de production d'un composé cyclique α-alcénylique utilisant le ligand.
PCT/JP2010/067279 2009-10-07 2010-10-01 LIGAND POUR CATALYSEUR DE SYNTHÈSE ASYMÉTRIQUE ET PROCÉDÉ POUR LA PRODUCTION D'UN COMPOSÉ CYCLIQUE α-ALCÉNYLIQUE L'UTILISANT WO2011043272A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002016249A1 (fr) * 2000-08-24 2002-02-28 Mitsubishi Denki Kabushiki Kaisha Filin en fibre synthetique pour ascenseurs
WO2002038628A2 (fr) * 2000-11-07 2002-05-16 Symyx Technologies, Inc. Ligands de pyridylamine substitues, complexes, catalyseurs et procedes pour la polymerisation, et polymeres
EP1308450A2 (fr) * 2001-11-06 2003-05-07 Symyx Technologies, Inc. Complexes d' amines et pyridyl substitués par titanium, catalyseurs et procédé de polymérisation d'éthylène et de styrène
WO2007129664A1 (fr) * 2006-05-02 2007-11-15 National University Corporation Nagoya University Ligand tétradentate chiral pour catalyse asymétrique et applications
WO2008085655A1 (fr) * 2007-01-08 2008-07-17 Exxonmobil Chemical Patents Inc. Procédés d'oligomérisation d'oléfines avec des catalyseurs à base de chrome, pyrine, mono-oxazoline

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR037228A1 (es) * 2001-07-30 2004-11-03 Dow Agrosciences Llc Compuestos del acido 6-(aril o heteroaril)-4-aminopicolinico, composicion herbicida que los comprende y metodo para controlar vegetacion no deseada

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002016249A1 (fr) * 2000-08-24 2002-02-28 Mitsubishi Denki Kabushiki Kaisha Filin en fibre synthetique pour ascenseurs
WO2002038628A2 (fr) * 2000-11-07 2002-05-16 Symyx Technologies, Inc. Ligands de pyridylamine substitues, complexes, catalyseurs et procedes pour la polymerisation, et polymeres
EP1308450A2 (fr) * 2001-11-06 2003-05-07 Symyx Technologies, Inc. Complexes d' amines et pyridyl substitués par titanium, catalyseurs et procédé de polymérisation d'éthylène et de styrène
WO2007129664A1 (fr) * 2006-05-02 2007-11-15 National University Corporation Nagoya University Ligand tétradentate chiral pour catalyse asymétrique et applications
WO2008085655A1 (fr) * 2007-01-08 2008-07-17 Exxonmobil Chemical Patents Inc. Procédés d'oligomérisation d'oléfines avec des catalyseurs à base de chrome, pyrine, mono-oxazoline

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
OHLOFF G. ET AL: "Preparation of tetrahydropyran and tetrahydrofuran derivatives from 1,7- and 1,6-allyl-diols, resp., by dehydration in the allyl position", HELVETICA CHIMICA ACTA, vol. 47, no. 2, 1964, pages 602 - 626 *
TANAKA S. ET AL: "Asymmetric Dehydrative Cyclization of omega-Hydroxy Allyl Alcohols Catalyzed by Ruthenium Complexes", ANGEWANDTE CHEMIE, INTERNATIONAL EDITION, vol. 48, no. 47, 9 November 2009 (2009-11-09), pages 8948 - 8951 *
TOMOAKI SEKI ET AL.: "omega-Hydroxy Allyl Alcohol-Rui no Shokubaiteki Fuseikanka", ANNUAL MEETING OF UNION OF CHEMISTRY-RELATED SOCIETIES IN CHUBU AREA, JAPAN YOKOSHU, vol. 40, 7 November 2009 (2009-11-07), pages 177 *

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